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1. Greater male than female variability in regional brain structure across the lifespan

Author

Erick J. Canales-Rodríguez, Hans J. Grabe, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Daniel Brandeis, Yang Wang, Henry Brodaty, Ruben C. Gur, Iris E. C. Sommer, Paul M. Thompson, Knut K. Kolskår, Christopher G. Davey, Dick J. Veltman, Eco J. C. de Geus, Tobias Banaschewski, Greig I. Zubicaray, Xavier Caseras, Sarah Baumeister, Raquel E. Gur, Vincent P. Clark, Maria J. Portella, Simon E. Fisher, Christopher R.K. Ching, Lars T. Westlye, Laura Koenders, Vince D. Calhoun, Carles Soriano-Mas, Nicholas G. Martin, Stefan Ehrlich, Fleur M. Howells, Catharina A. Hartman, Matthew D. Sacchet, Ole A. Andreassen, Josiane Bourque, Fabrice Crivello, Annette Conzelmann, Jaap Oosterlaan, Brenna C. McDonald, Gaelle E. Doucet, Avram J. Holmes, José M. Menchón, Danai Dima, Moji Aghajani, Joshua L. Roffman, Steven Williams, Lei Wang, David Mataix-Cols, Philip R. Szeszko, Bernd Weber, Tiril P. Gurholt, Sarah Hohmann, Ian H. Gotlib, Patricia Gruner, Anthony C. James, Paul Pauli, Lara M. Wierenga, Andrew M. McIntosh, Andrew J. Kalnin, Jim Lagopoulos, Henrik Walter, Andreas Reif, Andrew Simmons, Norbert Hosten, Pieter J. Hoekstra, Aristotle Voineskos, Alexander Tomyshev, Anton Albajes-Eizagirre, Jean-Paul Fouche, Dara M. Cannon, Ignacio Martínez‐Zalacaín, Geneviève Richard, Theophilus N. Akudjedu, David C. Glahn, Patricia J. Conrod, Ben J. Harrison, Alan Anticevic, Martine Hoogman, Francisco X. Castellanos, Bernd Kramer, Neda Jahanshad, Lieuwe de Haan, Dennis van der Meer, John D. West, Alan Breier, Jordan W. Smoller, P. G. P. Rosa, Katharina Wittfeld, Dan J. Stein, Jiyang Jiang, Jilly Naaijen, Christine Lochner, Dorret I. Boomsma, Alessandro Bertolino, Marise W. J. Machielsen, Hilleke E. Hulshoff Pol, Henry Völzke, Christian K. Tamnes, Ingrid Agartz, Georg C. Ziegler, Marieke Klein, Lars Nyberg, Perminder S. Sachdev, Philip Asherson, I.M. Veer, Sean N. Hatton, Núria Bargalló, Annabella Di Giorgio, Henk Temmingh, John A. Joska, Odile A. van den Heuvel, Wei Wen, Eveline A Crone, Kang Sim, Kathryn I. Alpert, Dennis van 't Ent, Jan K. Buitelaar, Joaquim Radua, Julian N. Trollor, B Mazoyer, Chaim Huyser, H. C. Whalley, Irina Lebedeva, Erin W. Dickie, Marcus Vinicus Zanetti, Stefan Borgwardt, Theodore D. Satterthwaite, Daniel H Wolf, Sophia I. Thomopoulos, Giulio Pergola, Luisa Lazaro, Ramona Baur-Streubel, Beathe Haatveit, Yannis Paloyelis, Ian B. Hickie, Jonna Kuntsi, Sophia Frangou, R. Salvador, Geraldo F. Busatto, Margaret J. Wright, Aurora Bonvino, Edith Pomarol-Clotet, Anouk den Braber, Lachlan T. Strike, Phil Lee, Anne Uhlmann, Yuliya N. Yoncheva, Mauricio H. Serpa, Dag Alnæs, Paola Fuentes-Claramonte, Katie L. McMahon, Andrew J. Saykin, Genevieve McPhilemy, Tiffany M. Chaim-Avancini, Sophie Maingault, Barbara Franke, Colm McDonald, Rachel M. Brouwer, Salvador Sarró, Department of Psychology, Education and Child Studies, Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, AMS - Ageing & Vitality, AMS - Sports, APH - Personalized Medicine, Cognitive Psychology, Clinical Neuropsychology, IBBA, Karolinska Schizophrenia Project (KaSP) Consortium, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Amsterdam Neuroscience, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Movement Disorder (MD), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Pediatric surgery, and Amsterdam Neuroscience - Brain Imaging

Subjects
Male, Netherlands Twin Register (NTR), SEGMENTATION, Vulnerability, Disease, HM, 0302 clinical medicine, Anàlisi de variància, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], sexual characteristics, Analysis of variance, nuclear magnetic resonance imaging, Cervell, Research Articles, Cerebral Cortex, Sex Characteristics, Radiological and Ultrasound Technology, 05 social sciences, Brain, clinical trial, Brain Structure, Magnetic Resonance Imaging, Early life, Adolescence, medicine.anatomical_structure, Neurology, Cerebral cortex, Healthy individuals, X-CHROMOSOME, anatomy & histology [Cerebral Cortex], Evolution of the brain, Female, Anatomy, Neurovetenskaper, Research Article, Radiology, Nuclear Medicine and Medical Imaging, Neuroinformatics, SEX-DIFFERENCES, diagnostic imaging, brain, Human Development, BF, Neuroimaging, SURFACE-AREA, Evolució del cervell, Regional area, Biology, MULTISAMPLE, 050105 experimental psychology, brain cortex, 03 medical and health sciences, CEREBRAL-CORTEX, Sex differences, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, human, ddc:610, Cortical surface, GENERAL INTELLIGENCE, diagnostic imaging [Brain], METAANALYSIS, biological variation, HUMAN HIPPOCAMPUS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], physiology [Biological Variation, Population], Neurosciences, Gender, Brain Cortical Thickness, multicenter study, Biological Variation, Population, Diferències entre sexes, physiology, RC0321, Radiologi och bildbehandling, Neurology (clinical), anatomy & histology [Brain], 170 000 Motivational & Cognitive Control, 030217 neurology & neurosurgery, anatomy and histology, meta analysis, physiology [Human Development], Demography
Abstract

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Published
2022

2. Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

Author

Zhiqiang Sha, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Boris Bernhardt, Sven Bolte, Geraldo F. Busatto, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Meiyu Duan, Fabio Luis Souza Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Jacqueline Fitzgerald, Dorothea L. Floris, Barbara Franke, Christine M. Freitag, Louise Gallagher, David C. Glahn, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Luisa Lazaro, Beatriz Luna, Jane McGrath, Sarah E. Medland, Filippo Muratori, Declan G. M. Murphy, Janina Neufeld, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Jose C. Pariente, Merel C. Postema, Karl Lundin Remnelius, Alessandra Retico, Pedro Gomes Penteado Rosa, Katya Rubia, Devon Shook, Kristiina Tammimies, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], University of Toronto, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Stockholm Health Care Services (SLSO), Curtin University [Perth], Planning and Transport Research Centre (PATREC), Universidade de São Paulo = University of São Paulo (USP), University of Pisa - Università di Pisa, Department of Child and Adolescent Psychiatry and Psychology, Centro de Investigación Biomédica en Red de Salut Mental (CIBER-SAM Network), Hospital Clinic Barcelona, King‘s College London, University Medical Center [Utrecht], Goethe-Universität Frankfurt am Main, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oregon Health and Science University [Portland] (OHSU), McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, and McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada]

Subjects
Neuroinformatics, Biochemistry & Molecular Biology, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], CHILDREN, ORGANIZATION, ACTIVATION, Cellular and Molecular Neuroscience, CONNECTIVITY, 130 000 Cognitive Neurology & Memory, CEREBRAL-CORTEX, Neural Pathways, Humans, HETEROGENEITY, Molecular Biology, 11 Medical and Health Sciences, Psychiatry, Cerebral Cortex, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, LANGUAGE LATERALIZATION, Neurosciences, Brain, 06 Biological Sciences, Magnetic Resonance Imaging, 17 Psychology and Cognitive Sciences, Psychiatry and Mental health, INDIVIDUALS, MORPHOMETRY, Neurosciences & Neurology, Life Sciences & Biomedicine, CORTICAL THICKNESS
Abstract

Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Published
2022

3. Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa : A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

Author

Esther Walton, Fabio Bernardoni, Victoria-Luise Batury, Klaas Bahnsen, Sara Larivière, Giovanni Abbate-Daga, Susana Andres-Perpiña, Lasse Bang, Amanda Bischoff-Grethe, Samantha J. Brooks, Iain C. Campbell, Giammarco Cascino, Josefina Castro-Fornieles, Enrico Collantoni, Federico D’Agata, Brigitte Dahmen, Unna N. Danner, Angela Favaro, Jamie D. Feusner, Guido K.W. Frank, Hans-Christoph Friederich, John L. Graner, Beate Herpertz-Dahlmann, Andreas Hess, Stefanie Horndasch, Allan S. Kaplan, Lisa-Katrin Kaufmann, Walter H. Kaye, Sahib S. Khalsa, Kevin S. LaBar, Luca Lavagnino, Luisa Lazaro, Renzo Manara, Amy E. Miles, Gabriella F. Milos, Alessio Maria Monteleone, Palmiero Monteleone, Benson Mwangi, Owen O’Daly, Jose Pariente, Julie Roesch, Ulrike H. Schmidt, Jochen Seitz, Megan E. Shott, Joe J. Simon, Paul A.M. Smeets, Christian K. Tamnes, Elena Tenconi, Sophia I. Thomopoulos, Annemarie A. van Elburg, Aristotle N. Voineskos, Georg G. von Polier, Christina E. Wierenga, Nancy L. Zucker, Neda Jahanshad, Joseph A. King, Paul M. Thompson, Laura A. Berner, Stefan Ehrlich, Walton, Esther, Bernardoni, Fabio, Batury, Victoria-Luise, Bahnsen, Klaa, Larivière, Sara, Abbate-Daga, Giovanni, Andres-Perpiña, Susana, Bang, Lasse, Bischoff-Grethe, Amanda, Brooks, Samantha J, Campbell, Iain C, Cascino, Giammarco, Castro-Fornieles, Josefina, Collantoni, Enrico, D'Agata, Federico, Dahmen, Brigitte, Danner, Unna N, Favaro, Angela, Feusner, Jamie D, Frank, Guido K W, Friederich, Hans-Christoph, Graner, John L, Herpertz-Dahlmann, Beate, Hess, Andrea, Horndasch, Stefanie, Kaplan, Allan S, Kaufmann, Lisa-Katrin, Kaye, Walter H, Khalsa, Sahib S, Labar, Kevin S, Lavagnino, Luca, Lazaro, Luisa, Manara, Renzo, Miles, Amy E, Milos, Gabriella F, Monteleone, Alessio Maria, Monteleone, Palmiero, Mwangi, Benson, O'Daly, Owen, Pariente, Jose, Roesch, Julie, Schmidt, Ulrike H, Seitz, Jochen, Shott, Megan E, Simon, Joe J, Smeets, Paul A M, Tamnes, Christian K, Tenconi, Elena, Thomopoulos, Sophia I, van Elburg, Annemarie A, Voineskos, Aristotle N, von Polier, Georg G, Wierenga, Christina E, Zucker, Nancy L, Jahanshad, Neda, King, Joseph A, Thompson, Paul M, Berner, Laura A, and Ehrlich, Stefan

Subjects
Anorexia Nervosa, Surface area, Cortical thickness, BMI, Thinness, MRI, Subcortical volume, Humans, Multicenter Studies as Topic, Prospective Studies, ddc:610, SDG 2 - Zero Hunger, Sensory Science and Eating Behaviour, Biological Psychiatry, VLAG, Cortical thickne, Cerebral Cortex, Thinne, Brain, Magnetic Resonance Imaging, Prospective Studie, Sensoriek en eetgedrag, Female, Human
Abstract

Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). Results: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. Conclusions: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Published
2022

4. Author Correction: Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Author

Merel C. Postema, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Geraldo Busatto Filho, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Adriana Di Martino, Ilan Dinstein, Fabio Luis S. Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Xin Feng, Jackie Fitzgerald, Dorothea L. Floris, Christine M. Freitag, Louise Gallagher, David C. Glahn, Ilaria Gori, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Xiang Zhen Kong, Luisa Lazaro, Jason P. Lerch, Beatriz Luna, Mauricio M. Martinho, Jane McGrath, Sarah E. Medland, Filippo Muratori, Clodagh M. Murphy, Declan G. M. Murphy, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Olga Puig, Alessandra Retico, Pedro Rosa, Katya Rubia, Devon Shook, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], University of Toronto, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Pisa - Università di Pisa, Department of Child and Adolescent Psychiatry and Psychology, Centro de Investigación Biomédica en Red de Salut Mental (CIBER-SAM Network), Hospital Clinic Barcelona, King‘s College London, NYU Langone Medical Center, Utrecht University [Utrecht], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oregon Health and Science University [Portland] (OHSU), School of Management, Fujian Agriculture and Forestry University (FAFU), and Goethe-University Frankfurt am Main

Subjects
Adult, Male, Adolescent, Autism Spectrum Disorder, Science, [SDV]Life Sciences [q-bio], Prefrontal Cortex, General Physics and Astronomy, Gyrus Cinguli, General Biochemistry, Genetics and Molecular Biology, Young Adult, Humans, Author Correction, Child, Cerebral Cortex, Multidisciplinary, Brain, Organ Size, General Chemistry, Autism spectrum disorders, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Case-Control Studies, Female, Neuroscience
Abstract

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

Published
2021

5. Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

Author

Jonathan P. Shock, Erika L. Nurmi, Francesco Benedetti, Gianfranco Spalletta, Anthony C. James, Damiaan Denys, Jose C. Pariente, Ignacio Martínez-Zalacaín, Yanni Liu, Paulo Marques, Joseph O'Neill, Ganesan Venkatasubramanian, Benjamin A. Ely, Noam Soreni, Tobias U. Hauser, Michael C. Stevens, Masaru Kuno, Kate D. Fitzgerald, Je-Yeon Yun, Stephanie H. Ameis, John Piacentini, Yuki Sakai, Kang Ik K. Cho, Kathrin Koch, Luciano Minuzzi, Fabrizio Piras, Hao Hu, Chaim Huyser, Philip R. Szeszko, Gerd Kvale, Zhen Wang, Luke Taylor, Jean Paul Fouche, Marcelo Q. Hoexter, Francesca Assogna, Odile A. van den Heuvel, Rachel Marsh, Carles Soriano-Mas, Alan Anticevic, David Mataix-Cols, Eiji Shimizu, Fern Jaspers-Fayer, Rajat M. Thomas, Yoshinari Abe, Pedro Moreira, Norbert Kathmann, Astrid Morer, Rosa Calvo, Guido van Wingen, João Ricardo Sato, Egill A. Fridgeirsson, Chris Perriello, Janardhanan C. Narayanaswamy, Anushree Bose, Pedro Morgado, Oana G. Rus-Oswald, Akiko Nakagawa, Silvia Brem, Luisa Lazaro, Dan J. Stein, Paul D. Arnold, Yoshiyuki Hirano, Premika S.W. Boedhoe, Emily R. Stern, Irene Bollettini, Sara Dallaspezia, Lianne Schmaal, Federica Piras, Willem B Bruin, José M. Menchón, Jan K. Buitelaar, Christian Kaufmann, Christine Lochner, Yuqi Cheng, Brian P. Brennan, H. Blair Simpson, David F. Tolin, Daan van Rooij, Pino Alonso, Iliyan Ivanov, S. Evelyn Stewart, Paul M. Thompson, Takashi Nakamae, Deniz A. Gürsel, Paul Zhutovsky, Jan C. Beucke, Jamie D. Feusner, Patricia Gruner, Tomohiro Nakao, Y.C. Janardhan Reddy, Jun Soo Kwon, Graduate School, ANS - Compulsivity, Impulsivity & Attention, APH - Global Health, APH - Mental Health, Adult Psychiatry, Child Psychiatry, Bruin, Willem B., Taylor, Luke, Thomas, Rajat M., P Shock, Jonathan, Zhutovsky, Paul, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Assogna, Francesca, Benedetti, Francesco, Beucke, Jan C., Boedhoe, Premika S. W., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P., K Buitelaar, Jan, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K., Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A., Feusner, Jamie D., Fitzgerald, Kate D., Fouche, Jean-Paul, Fridgeirsson, Egill A., Gruner, Patricia, Gürsel, Deniz A., Hauser, Tobias U., Hirano, Yoshiyuki, Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ivanov, Iliyan, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Soo Kwon, Jun, Liu, Yanni, Lochner, Christine, Lázaro, Luisa, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M., Minuzzi, Luciano, Moreira, Pedro S., Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nurmi, Erika L., O’Neill, Joseph, Pariente, Jose C., Perriello, Chri, Piacentini, John, Piras, Fabrizio, Piras, Federica, Janardhan Reddy, Y. C., Rus-Oswald, Oana G., Sakai, Yuki, Sato, João R., Schmaal, Lianne, Shimizu, Eiji, Blair Simpson, H., Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Evelyn Stewart, S., Szeszko, Philip R., Tolin, David F., Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, van Rooij, Daan, Consortium, ENIGMA-OCD, Thompson, Paul M., van den Heuvel, Odile A., Stein, Dan J., van Wingen, Guido A., Netherlands Institute for Neuroscience (NIN), ENIGMA-OCD Working Group, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Psychiatry

Subjects
Obsessive-Compulsive Disorder, Multivariate analysis, Disease, Neuroimaging biomarkers, 0302 clinical medicine, Obsessive-compulsive disorder, Medicine, Psychology, Prefrontal cortex, screening and diagnosis, medicine.diagnostic_test, Biochemical markers, Brain, Serious Mental Illness, Magnetic Resonance Imaging, 3. Good health, Psychiatry and Mental health, Detection, Mental Health, Marcadors bioquímics, Public Health and Health Services, Biomedical Imaging, Clinical psychology, medicine.drug, medicine.medical_specialty, Clinical Sciences, MEDLINE, Neuroimaging, Article, lcsh:RC321-571, Cellular and Molecular Neuroscience, 03 medical and health sciences, Obsessive compulsive, Clinical Research, Internal medicine, Medical imaging, Diagnostic biomarker, Humans, Clinical significance, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Fluoxetine, business.industry, Neurosi obsessiva, Neurosciences, Magnetic resonance imaging, Diagnostic markers, 030227 psychiatry, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Obsessive compulsive disorder, ENIGMA-OCD Working Group, business, 030217 neurology & neurosurgery, Biomarkers, Neuroscience
Abstract

ObjectiveNo diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Magnetic resonance imaging (MRI) studies have provided evidence for structural abnormalities in distinct brain regions, but effect sizes are small and have limited clinical relevance. To investigate whether individual patients can be distinguished from healthy controls, we performed multivariate analysis of structural neuroimaging data from the ENIGMA-OCD consortium.MethodWe included 46 data sets with neuroimaging and clinical data from adult (≥18 years) and pediatric (1images from 2,304 OCD patients and 2,068 healthy controls were analyzed using standardized processing to extract regional measures of cortical thickness, surface area and subcortical volume. Machine learning classification performance was tested using cross-validation, and possible effects of clinical variables were investigated by stratification.ResultsClassification performance for OCD versus controls using the complete sample with different classifiers and cross-validation strategies was poor (AUC—0.57 (standard deviation (SD)=0.02;Pcorr=0.19) to 0.62 (SD=0.03;Pcorrcorr>.99) to 0.54 (SD=0.08;Pcorr>.99)). In contrast, good classification performance (>0.8 AUC) was achieved within subgroups of patients split according to their medication status.ConclusionsParcellated structural MRI data do not enable good distinction between patients with OCD and controls. However, classifying subgroups of patients based on medication status enables good identification at the individual subject level. This underlines the need for longitudinal studies on the short- and long-term effects of medication on brain structure.

Published
2020

6. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author

Xiang-Zhen Kong, Premika S.W. Boedhoe, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Francesca Assogna, Justin T. Baker, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Brian P. Brennan, Jan Buitelaar, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Damiaan Denys, Benjamin A. Ely, Jamie Feusner, Kate D. Fitzgerald, Jean-Paul Fouche, Egill A. Fridgeirsson, David C. Glahn, Patricia Gruner, Deniz A. Gürsel, Tobias U. Hauser, Yoshiyuki Hirano, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Anthony James, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Masaru Kuno, Gerd Kvale, Jun Soo Kwon, Luisa Lazaro, Yanni Liu, Christine Lochner, Paulo Marques, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Sarah E. Medland, José M. Menchón, Luciano Minuzzi, Pedro S. Moreira, Astrid Morer, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Joseph O'Neill, Jose C. Pariente, Chris Perriello, John Piacentini, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y.C. Janardhan Reddy, Oana Georgiana Rus-Oswald, Yuki Sakai, Joao R. Sato, Lianne Schmaal, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, David F. Tolin, Aki Tsuchiyagaito, Daan van Rooij, Guido A. van Wingen, Ganesan Venkatasubramanian, Zhen Wang, Je-Yeon Yun, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Clyde Francks, Alan Anticevic, Nerisa Banaj, Nuria Bargalló, Daniel Brandeis, Geraldo F. Busatto, Anna Calvo, Valentina Ciullo, Froukje E. de Vries, Stella J. de Wit, Erin Dickie, Renate Drechsler, Madalena Esteves, Andrea Falini, Yu Fang, Martijn Figee, Martine Fontaine, Geoff Hall, Sayo Hamatani, Gregory L. Hanna, Bjarne Hansen, Keisuke Ikari, Neda Jahanshad, Ricardo Magalhães, Yasutaka Masuda, Koji Matsumoto, James T. McCracken, Euripedes C. Miguel, Jin Narumoto, Seiji Nishida, Sara Poletti, Tim Reess, Eiji Shimizu, Nuno Sousa, Jumpei Takahashi, Jinsong Tang, Anders Lillevik Thorsen, Ysbrand D. van der Werf, Dick J. Veltman, Daniela Vecchio, Susanne Walitza, Anri Watanabe, Jian Xu, Xiufeng Xu, Kei Yamada, Tokiko Yoshida, Mojtaba Zarei, Qing Zhao, Cong Zhou, ENIGMA-OCD Working Group, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, Kong, X. -Z., Boedhoe, P. S. W., Abe, Y., Alonso, P., Ameis, S. H., Arnold, P. D., Assogna, F., Baker, J. T., Batistuzzo, M. C., Benedetti, F., Beucke, J. C., Bollettini, I., Bose, A., Brem, S., Brennan, B. P., Buitelaar, J., Calvo, R., Cheng, Y., Cho, K. I. K., Dallaspezia, S., Denys, D., Ely, B. A., Feusner, J., Fitzgerald, K. D., Fouche, J. -P., Fridgeirsson, E. A., Glahn, D. C., Gruner, P., Gursel, D. A., Hauser, T. U., Hirano, Y., Hoexter, M. Q., Hu, H., Huyser, C., James, A., Jaspers-Fayer, F., Kathmann, N., Kaufmann, C., Koch, K., Kuno, M., Kvale, G., Kwon, J. S., Lazaro, L., Liu, Y., Lochner, C., Marques, P., Marsh, R., Martinez-Zalacain, I., Mataix-Cols, D., Medland, S. E., Menchon, J. M., Minuzzi, L., Moreira, P. S., Morer, A., Morgado, P., Nakagawa, A., Nakamae, T., Nakao, T., Narayanaswamy, J. C., Nurmi, E. L., O'Neill, J., Pariente, J. C., Perriello, C., Piacentini, J., Piras, F., Pittenger, C., Reddy, Y. C. J., Rus-Oswald, O. G., Sakai, Y., Sato, J. R., Schmaal, L., Simpson, H. B., Soreni, N., Soriano-Mas, C., Spalletta, G., Stern, E. R., Stevens, M. C., Stewart, S. E., Szeszko, P. R., Tolin, D. F., Tsuchiyagaito, A., van Rooij, D., van Wingen, G. A., Venkatasubramanian, G., Wang, Z., Yun, J. -Y., Anticevic, A., Banaj, N., Bargallo, N., Brandeis, D., Busatto, G. F., Calvo, A., Ciullo, V., de Vries, F. E., de Wit, S. J., Dickie, E., Drechsler, R., Esteves, M., Falini, A., Fang, Y., Figee, M., Fontaine, M., Hall, G., Hamatani, S., Hanna, G. L., Hansen, B., Ikari, K., Jahanshad, N., Magalhaes, R., Masuda, Y., Matsumoto, K., Mccracken, J. T., Miguel, E. C., Narumoto, J., Nishida, S., Poletti, S., Reess, T., Shimizu, E., Sousa, N., Takahashi, J., Tang, J., Thorsen, A. L., van der Werf, Y. D., Veltman, D. J., Vecchio, D., Walitza, S., Watanabe, A., Xu, J., Xu, X., Yamada, K., Yoshida, T., Zarei, M., Zhao, Q., Zhou, C., Thompson, P. M., Stein, D. J., van den Heuvel, O. A., Francks, C., Netherlands Institute for Neuroscience (NIN), Universidade do Minho, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Psychiatry

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Obsessive-Compulsive Disorder, Mega-analysis, Mega-analysi, media_common.quotation_subject, Thalamus, Medicina Básica [Ciências Médicas], Audiology, Asymmetry, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, mental disorders, medicine, Image Processing, Computer-Assisted, Obsessive-compulsive disorder, Brain asymmetry, Humans, Child, Biological Psychiatry, Depression (differential diagnoses), media_common, Brain Mapping, Science & Technology, medicine.diagnostic_test, business.industry, Laterality, Neurosi obsessiva, Brain, Magnetic resonance imaging, Cerebral cortex, Magnetic Resonance Imaging, humanities, Escorça cerebral, 030104 developmental biology, Meta-analysis, Ciências Médicas::Medicina Básica, Pallidum, Anxiety, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Accepted Manuscript, BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -20.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD., This research was funded by the Max Planck Society (Germany). Additional funding was from the Japan Society for the Promotion of Science (KAKENHI Grant No. 18K15523 [to YA], KAKENHI Grant No. 16K04344 [to YH], KAKENHI Grant Nos. 16K19778 and 18K07608 [to TNakam], and KAKENHI Grant No. 26461762 [to AN]); the Carlos III Health Institute (Grant No. PI14/00419 [to PA], Grant No. PI040829 cofunded by European Regional Development Fund [to LL], Grant No. FI17/00294 [to IM-Z], Grant No. PI16/00950 [to JMM], and Grant Nos. CPII16/00048, PI13/01958, and PI16/00889 cofunded by European Regional Development Funds [to CS-M]); the Ontario Mental Health Foundation (Research Training Fellowship [to SHA]); Alberta Innovates Translational Health Chair in Child and Youth Mental Health (to PDA), the Ontario Brain Institute (to PDA); the National Institute of Mental Health (Grant No. K23MH104515 [to JTB], Grant No. K23-MH092397 [to BPB], Grant No. K23MH082176 [to KDF), Grant No. R21MH101441 [to RM], Grant No. R01MH081864 [to JO and JP], and Grant No. R01MH085900 [to JO and JF], Grant No. R21MH093889 [to HBS]); Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant No. 2011/21357–9 [to MCB], Grant No. 2011/21357–9 [to GFB], Grant No. 2011/21357–9 [to MQH], and Grant No. 2011/21357–9 [to ECM]); the Swiss National Science Foundation (Grant No. 320030_130237 [to SB; principal investigator, Susanne Walitza]); the Hartmann Müller Foundation (Grant No. 1460 [to SB]); the David Judah Fund at the Massachusetts General Hospital (to BPB); EU FP7 Project TACTICS (Grant No. 278948 [to JB]); the National Natural Science Foundation of China (Grant No. 81560233 [to YC] and Grant No. 81371340 [to ZW]); the International OCD Foundation (Grant No. K23 MH115206 [to PG]); the Wellcome Sir Henry Dale Fellowship (Grant No. 211155/Z/18/Z [to TUH]); the Jacobs Foundation (to TUH); the Brain and Behavior Research Foundation (2018 NARSAD Young Investigator Grant No. 27023 [to TUH]); the Agency for Medical Research and Development (Grant No. JP18dm0307002 [to YH]); the Michael Smith Foundation for Health Research (to FJ-F); the Federal Ministry of Education and Research of Germany (Grant No. BMBF-01GW0724 [to NK]); the Deutsche Forschungsgemeinschaft (Grant No. KO 3744/7–1 [to KK]); the Helse Vest Health Authority (Grant Nos. 911754 and 911880 [to GK]); the Norwegian Research Council (Grant No. HELSEFORSK 243675 [to GK]); the Marató TV3 Foundation (Grant Nos. 01/2010 and 091710 [to LL]); the Agency for Management of University and Research Grants (Grant No. 2017 SGR 881 [to LL] and 2017 SGR 1247 from the Generalitat de Catalunya [to JMM]); Fundação para a Ciência e a Tecnologia (Grant No. PDE/BDE/113604/2015 from the PhD-iHES Program [to RM], Grant No. PDE/BDE/113601/2015 from the PhD-iHES Program [to PSM]); the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research (Grant Nos. 22591262, 25461732, and 16K10253 [to TNakao]); the Government of India Department of Science and Technology (DST INSPIRE Faculty Grant No. -IFA12-LSBM-26 [to JCN] and Grant No. SR/S0/HS/0016/2011 [to YCJR]); the Government of India Department of Biotechnology (Grant No. BT/06/IYBA/2012 [to JCN] and Grant No. BT/PR13334/Med/30/259/2009 [to YCJR]); the New York State Office of Mental Health (to HBS); the Italian Ministry of Health (Grant No. RC13-14-15-16A [to GS]); the National Center for Advancing Translational Sciences (Grant No. UL1TR000067/KL2TR00069 [to ERS]); the Canadian Institutes of Health Research (to SES); the Michael Smith Foundation for Health Research (to SES); the British Columbia Provincial Health Services Authority (to SES); the Netherlands Organization for Scientific Research (Grant No. NWO/ZonMW Vidi 917.15.318 [to GAvW]); the Wellcome-DBT India Alliance (Grant No. 500236/Z/11/Z [to GV]); the Shanghai Key Laboratory of Psychotic Disorders (Grant No. 13dz2260500 [to ZW]).

Published
2020

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